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Djurdjević was born in Koblenz, West Germany. As a child he exhibited a talent for drawing, inspired by cartoons such as He-Man. When Marko was 11, he discovered Burne Hogarth's book Dynamic Anatomy (1958), a major turning point in his self-education. Studying the guide for two years, Djurdjevic then put the book away and began to add a layer of realism to his drawings. He used what he learned from Hogarth as a foundation, while at the same time pulling ideas from his everyday life observations.

As a teenager, Djurdjević became influenced by American comic books such as Spider-Man, a foreshadowing of his later career as a Marvel Comics illustrator. He rejected the comic style of drawing a couple of years later, citing it as "too stylized" and "exaggerated", which was contrary to his training early on. At the age of 17, Marko began working professionally as an illustrator. He mostly produced black and white drawings for tabletop rpg companies such as White Wolf, Inc. and FanPro Games.

Djurdjević continued working in Germany as an illustrator for the next few years, building upon his personal style which took on an almost sketch-like quality while retaining anatomical accuracy. He was convinced by a friend to begin posting some of his designs and pictures on a relatively new online art community called conceptart.org. He gained immediate recognition for his ability to conjure extremely believable figures from his imagination in a short amount of time. Djurdjević's popularity was noticed by the founding members of conceptart.org, Jason Manley and Andrew Jones. The two had been creating a network of friends through their website, and were in the process of forming a company devoted to producing concept art for videogame companies and the film industry. Djurdjević was offered a position in the group as a senior concept artist, focusing on human character and creature design. He accepted and became one of the original members of the company now known as Massive Black.

Massive Black started off as a group of professionals who collaborated over the internet. As more projects developed, the company was forced to create a physical headquarters in San Francisco, California. Djurdjevic left his home country and moved to the U.S., where he resided for the next 3½ years. During this time, the conceptart.org community leaders and professional instructors began to hold workshops in various locations, with the intention of teaching fledgling artists directly. This served as a way of connecting with the artistic community that the website had formed on a more intimate level.

In 2004, Djurdjević was contacted by Christian Gunther to work on a post-apocalyptic themed rpg known as Degenesis. Gunther had previously released the game in 2001, but it received little attention. Gunther was hoping that a revision of the game, along with a strong artistic direction, would give the game a larger audience. Djurdjević was commissioned to design most of the game's look, as well as the bulk of its interior artwork and character designs. This project allowed Djurdjević to showcase his ability to create original, yet believable worlds on a large scale. He quickly became associated with the style of the characters in the game, with their asymmetrical designs, horrific themes, and focus on gesture. Marko often stated that the post-apocalyptic genre was his favorite genre to work in.

Djurdjević continued to work in California as a concept artist for the next few years. The founders of the conceptart.org website decided to start developing tutorial DVD's that could be sold to the general public. Marko was asked to be the first artist to produce a DVD, showcasing his process and intuitive ability to create game characters from start to finish. He accepted. Around this time, Djurdjević (at the urging of his friend Nic Klein), re-created 18 characters from a long-time favorite series of theirs, the X-Men. Djurdjevic finished the drawings in a mere three days, and posted them on the conceptart.org forums. The response was huge, and Djurdjević was immediately flooded with fan and hate mail over the creations. The designs increased his popularity online, and the characters were eventually discovered by an editor working at Marvel Comics. The sketches were well received by the company, so they contacted Djurdjević and offered him an exclusive contract to produce illustrations for some of their title's covers. He accepted the offer after producing a test cover for the series X-23.

At the end of 2006, Massive Black released the DVD Character Ideation. This event cemented Djurdjević as a world-renowned artist.